巨核细胞生成的调控。

Haemostasis Pub Date : 1999-09-01 DOI:10.1159/000022458
J P Caen, Z C Han, S Bellucci, M Alemany
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引用次数: 10

摘要

经过35年的研究,血小板产生的生理调节因子已经确定,重组蛋白是可用的。随着血小板生成素(TPO)的发现,人们期待其在各种临床巨核细胞和血小板疾病中的潜在应用,并开展了临床试验。迄今为止,令人鼓舞的临床前研究报告表明,与促红细胞生成素或G-CSF一样,可以预期毒性最小。TPO潜在的限制性副作用可能是血栓形成。然而,要知道这种细胞因子是否对危及生命的血小板减少症患者(如接受骨髓移植或接受高剂量化疗的患者)具有重要的治疗意义还为时过早。确定TPO在预防或改善出血方面的疗效仍需要进行一些实验和临床研究,这是合理使用具有止血作用的细胞因子的最终目标。巨核细胞生成调节因子的基础和临床研究进展迅速。现在,毫无疑问,其中一些调节剂在纠正各种病因的造血障碍方面是有效的。负调节因子的研究不仅对了解巨核细胞生成在正常和病理状态下的调控具有重要意义,而且具有潜在的临床应用价值。其中一些调节剂已被证明对治疗原发性血小板增多症和其他骨髓增生性疾病有效。血小板因子4 (PF4)和一些其他趋化因子也能够保护祖细胞免受化疗药物的细胞毒性。然而,仍然需要进行详细的研究,以确定这些调节剂的确切作用机制,并建立单独使用负调节剂或与正调节剂联合使用的最佳临床方案,以治疗各种血液病和癌症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of megakaryocytopoiesis.

After 35 years of research, a physiological regulator of platelet production has been identified and the recombinant protein is available. With the discovery of thrombopoietin (TPO), its potential use in a wide variety of clinical megakaryocytic and platelet disorders has been expected and clinical trials have been undertaken. To date, the reported encouraging pre-clinical studies indicate that, as with erythropoietin or G-CSF, minimal toxicity can be expected. A potential limiting side-effect of TPO could be the induction of thrombosis. Nevertheless, it is too early to know whether this cytokine will be of major therapeutic importance for patients with life-threatening thrombocytopenia, such as patients undergoing bone marrow transplantation or subjected to a high dose of chemotherapy. Several experimental and clinical studies are still needed to determine the efficacy of TPO in the prevention or the amelioration of bleeding, which is the ultimate goal for the appropriate use of cytokines with haemostatic benefit. Basic and clinical studies on regulators of megakaryocytopoiesis have rapidly progressed. Now, there is no doubt that some of these regulators are effective in correcting haematopoietic disorders of various aetiologies. Studies on negative regulators not only are important to understand the regulation of megakaryocytopoiesis in normal and pathological states but also have a potential clinical application. Some of these regulators have been shown to be effective in the treatment of essential thrombocythaemia and other myeloproliferative disorders. Platelet factor 4 (PF4) and some other chemokines are also capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs. However, detailed investigations are still required to determine the precise mechanism(s) of action of these regulators and to establish the optimal clinical protocols of negative regulators alone or in association with positive regulators for the treatment of various haematological diseases and cancer.

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